Overview and Background: This amended K-23 application focuses on developing an expertise in clinical trials for cancer-related symptoms. One prevalent cancer-related symptom, depression, can occur throughout the course of illness and into survivorship. Although treatment with antidepressants is common, major gaps exist in our current state of the science and few studies exist to support these clinical practices. This award will address one such gap, evidence for the efficacy of antidepressants for major depression comorbid with cancer, by completing a placebo-controlled trial in an oncology population, now individuals with advanced non-small cell lung cancer (NSCLC), as part of rigorous program of training in clinical trials and psychosocial oncology research methodology. Environment: The study will take place at the Massachusetts General Hospital (MGH) Cancer Center, merging the resources of the MGH Department of Psychiatry, which encompasses the Depression Clinical and Research Program (DCRP), the Division of Psychiatry and Medicine, and the Behavioral Medicine Service;Dana-Farber/Partners CancerCare;and the Harvard School of Public Health (HSPH). Career Development Plan: Training will emphasize skills necessary for designing, conducting, and analyzing clinical trials for the management of cancer-related symptoms. The beginning of the award period will emphasize coursework, consultation and further shaping of the research project, and the last two years of the award will be used to develop an R01 application to continue related research. Intensive coursework in statistics and quantitative methods at the HSPH will lead to an MPH. At MGH, mentorship and research training will obtained through the DCRP (Drs. Fava and Nierenberg), the MGH Division of Psychiatry and Medicine (Drs. Fricchione and Greenberg), the MGH Cancer Center (Drs. Chabner and Lynch), and experts in biostatistical analysis and clinical trial design (Drs. Safren and Schoenfeld). External to MGH, the training will include consultations in psychosocial oncology research from experts at Memorial Sloan-Kettering Cancer Center (Drs.Breitbart and Roth) and the Dana-Farber Cancer Institute (Dr. Kornblith). Research Plan: The study is an adequately powered eight-week randomized, placebo-controlled trial of an antidepressant, escitalopram, for major depressive disorder in people with advanced NSCLC. Secondary goals include evaluating tolerability and investigating moderators of treatment response.